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New Hope for Thalassemia Sufferers

The blood disorder, Thalassemia is very prevalent among the Kadazandusuns.

Last month I donated blood in support of a 30+ year old thalassemic girl who lives just 3 houses next to mine. She has had blood transfusions since small but since she had bone marrow transplant she had the joy of enjoying her thirties age. Hopefully she will enjoy many more, especially at this time when the promise of new technologies offers brighter hopes for a better cure.

In a 2008 study headed by a researcher from the Faculty of Medicine, University of Malaya, from 125 blood samples obtained from unrelated Kadazandusuns, α- and β-thalassemia were confirmed at 33.6% and 12.8%. In another study it was found that from all the ethnic groups studied in Sabah, Kadazandusuns showed the highest prevalence for this disease.

Thalassemia is an inherited blood disorder in which the body makes an abnormal form of hemoglobin, the protein molecule found in red blood cells. The disorder results in excessive destruction of red blood cells, which leads to anemia. It is caused by either a genetic mutation or a deletion of certain key gene fragments. There are two main forms of thalassemia which are serious: In alpha thalassemia, at least one of the alpha globin genes has a mutation or abnormality, and in beta thalassemia, the beta globin genes are affected.

People with thalassemia can get sick from an overload of iron in their bodies, either from the disease itself or from frequent blood transfusions. Young children, even with blood transfusions, are not expected to reach beyond their teen years because of this disease. Bone marrow transplantation—or in more detail, the blood-making stem cells (hematopoietic stem cells) found in bone marrow, but more of this later)?—may offer the only possibility (so far) of a cure in young people who have an HLA-matched donor. Success rates have been in the 80–90% range.

If you recalled, the root cause of thalassemia is the inability of the body to make either one of two proteins that makes haemoglobin, and that deficiency arose because the sufferer’s crucial deletion or mutation in his/her genome (genes that codes for the making of the protein(s). But, what if somehow those missing/bad genes can be corrected? What if it is possible, much like a software programmer can edit his code, to shift though the 3 billion plus of DNA code pairs in the human genome, zero in on the flawed part, delete it, and replace with the right and healthy one?

Enter CRISPR (Clustered regularly interspaced short palindromic repeats) technology, a new method of targeted gene modification discovered not more than 5 years ago. More specifically known as CRISPR/Cas9, this technology makes it possible to do genome editing – the precise and targeted modification of the genetic material of cells. Genome editing works by using an enzyme to make a cut at a particular sequence in the genome, followed by the deletion, repair or insertion of genetic material at the cut site.

Can CRISPR genome editing pave the way for a better and safer cure for thalassemia? Sci-fi wishful thinking? Think again.

Today (2nd August in the U.S.), it was reported in the Washington Post that scientists have successfully undertaken gene editing in the first human embryo CRISPR experiment in U.S. to corrects gene for an inherited heart disease, hypertrophic cardiomyopathy. This method of genome editing and repair has already been found to work in a mouse with the β-thalassemia defective gene, with “sustained elevation of blood haemoglobin levels into the normal range, reduced reticulocytosis, [and] reversal of splenomegaly “. In 2015 a team of Chinese scientists, using the same technology, reported that their success rate was one in four for β-thalassemia genetically abnormal human embryos although they did raised their concerns about off-target effects. Just last march, Intellia Therapuetics, a company dedicated to developing potentially curative genome editing treatments, together with healthcare global giant, Novartis, have announced that their hematopoietic stem cell transplant (read “thalassemia” here) program is planned to undertake the first human clinical study next year. A different company, CRISPR Therapeutic is also targeting human clinical trials for β-thalassemia treatments with about the same timeline.

Here’s praying for my neighbour. And for my cousin-in-law, who is a carrier of the thalassemia gene.